A later heading date generally leads to higher grain yield in favorable ecological regions;however,grain yield reaches a limit as the heading date exceeds a certain threshold.Ghd7 is the first cloned major gene that r...A later heading date generally leads to higher grain yield in favorable ecological regions;however,grain yield reaches a limit as the heading date exceeds a certain threshold.Ghd7 is the first cloned major gene that regulates heading date,plant height and grain number.Here,we investigated the relationship between Ghd7 and florigen genes Hd3a and RFT1,to determine their roles in regulating heading date and grain number under different photoperiods.Our results revealed that under long-day(LD)conditions,Hd3a acts prior to RFT1 to promote heading while negatively regulating plant height and grain number.In contrast,Ghd7 positively regulates heading date,plant height,and grain number by inhibiting both Hd3a and RFT1.Under short-day(SD)conditions,the functions of Hd3a and RFT1 remain consistent with those under LD conditions,but Ghd7 does not inhibit their expression,resulting in a weaker phenotypic effect compared to Hd3a.Additionally,under both LD and SD conditions,increased Ghd7 expression enhances its inhibitory effect on Hd3a and RFT1,leading to later heading and increased grain number;however,once the heading date exceeds 94 d,grain number no longer increases.Moreover,the gn1a allele increased grain number by 16.5%to 42.5%,while combinations of the elite alleles from Ghd7,Hd3a,RFT1,and Gn1a significantly increased grain number by up to 240.9%.Therefore,we propose a new breeding strategy to optimize the heading date and grain number using the Ghd7Hd3aRFT1gn1a combination of Ghd7,Hd3a,RFT1,and Gn1a under LD conditions,and the Ghd7hd3aRFT1gn1a combination under SD conditions.This strategy improved the yield of the high-quality Northeast variety Kongyu 131(KY131)by 69.1%in Beijing and 93.7%in Hainan.This strategy will greatly improve the efficiency of north-to-south adaptation in rice,providing theoretical guidance for expanding the geographical adaptability of rice varieties.展开更多
Recently,Choe-Koo-Wang(J Funct Anal,2020,278)demonstrated the rigid phenomenon:The compact linear combination of composition operators under the Coefficient Non-cancellation Condition(CNC),implies that each difference...Recently,Choe-Koo-Wang(J Funct Anal,2020,278)demonstrated the rigid phenomenon:The compact linear combination of composition operators under the Coefficient Non-cancellation Condition(CNC),implies that each difference is compact on the weighted Bergman space in the unit disk.Motivated by the subtle connection of composition operator theory on the weighted Bergman spaces,Korenblum spaces and bounded holomorphic function spaces,we first explore the rigid phenomenon which also holds on the Korenblum space over the unit ball.Furthermore,we discuss which difference of composition operators is compact when the compact combination of composition operators does not satisfy the condition(CNC)on Korenblum spaces and bounded holomorphic function spaces over the unit ball setting.展开更多
Understanding the mechanical properties of coal-rock-bolt(CRB)combinations at high strain rates and the anchoring mechanism of bolts is crucial for ensuring the safety of coal mining operations.However,the dynamic beh...Understanding the mechanical properties of coal-rock-bolt(CRB)combinations at high strain rates and the anchoring mechanism of bolts is crucial for ensuring the safety of coal mining operations.However,the dynamic behaviors of these combinations,especially the mechanism of action of prestressed bolts,still need to be further investigated.This study carried out split Hopkinson pressure bar(SHPB)tests on three sets of coal-rock(CR),CRB,and coal-rock-prestressed bolt(CRPB)combinations with different interface angles(β=15°,30°,45°,and 60°).The dynamic properties of the combinations were analyzed based on the stress-strain curve,energy dissipation,dynamic strength,fractal dimension of cracks,and failure mode of bolts.The test results show that a larger β will affect the stress transfer and anti-sliding ability of CR,resulting in a decrease in CR strength.The anchoring force of the bolt effectively suppresses the slip feature of CRB at the yield stage.As the strain rate increases,CRB shows a more pronounced'sudden increase'in strength,and the bolt significantly enhances its dynamic strength.The prestressed bolts enhance the dynamic strength of CRPB while weaken the effect of β.The fractal dimension of the macrocracks increases with strain rate,with smaller variations in CRB and CRPB,indicating that the bolt reduces the complexity degree of CRB and CRPB.The anchoring force of CRB depends on bolt strength,which reduces the slip along the interface.The anchoring force of CRPB balances the coal-rock slip and suppresses crack formation,resulting in a more cohesive response under dynamic load.展开更多
Effective isolation between the cement sheath and the sandstone is crucial for the development and production of oil and gas wells in sandstone formations.In this study,a cement-sandstone composite(CSC)was prepared,an...Effective isolation between the cement sheath and the sandstone is crucial for the development and production of oil and gas wells in sandstone formations.In this study,a cement-sandstone composite(CSC)was prepared,and based onμ-CT three-dimensional reconstruction imaging and finite element analysis(FEA)techniques,the stress distribution and potential failure mechanism at the cement-sandstone bonding interface under axial loading were analyzed.The key findings are as follows:(1)stress concentrations are highly likely to form at the gap between the cement and sandstone interface and around interfacial voids,with Von Mises stress reaching critical levels of 18.0-20.0 MPa at these locations,significantly exceeding the stress magnitudes in well-bonded regions;(2)the phenomenon of local stress concentration driven by interfacial defects can be identified as the main basis for predicting damage location in interfacial debonding and continuous shear under axial load;(3)ensuring tight cementation at the cement-sandstone interface and minimizing interfacial voids are paramount for preventing stress-induced failure;(4)the critical Von Mises stress value of 20 MPa at the interface defect can be used as a benchmark for material selection and designed to ensure long-term integrity in oil and gas well applications subjected to similar axial loads.These findings contribute to a more accurate understanding of the failure mechanism of the cement-sandstone interface and to the precise design of material properties,thereby ensuring the long-term integrity of oil and gas well applications subjected to similar axial loads.展开更多
Objective To observe the influence of different acupoint combinations on immediate effect of surface electromyography of patients with cervical spondylosis, and to explore the interactions and laws among different acu...Objective To observe the influence of different acupoint combinations on immediate effect of surface electromyography of patients with cervical spondylosis, and to explore the interactions and laws among different acupoint combinations. Methods Acupuncture in three kinds of different acupoint combinations was conducted on 90 patients with cervical spondylosis（three groups）： group A [distal point selection group： Kūnlún（昆仑 BL 60） and Hòuxī（后溪 SI 3）]; group B [local point selection group： Fēngchí（风池 GB 20） and Tiānzhù（天柱 BL 10）]; group C（distal and local point selection group： BL 60, SI 3, GB 20 and BL 10）. Self control before and after treatment was adopted to observe the mean value of surface electromyography（SEMG） amplitude, to measure the mean values of integrated electromyography（IEMG） and electromyography root mean square（RMS）, and to calculate the variation rate of electromyography amplitude of trapezius on the affected side of patients before and after acupuncture. The differences of influences of different acupoint combinations on immediate effect of surface electromyography were compared intra-group, and the differences among the three groups after acupuncture were also compared. Results According to the intragroup comparison before and after acupuncture, the differences of mean value of electromyography amplitude, variation rate of electromyography amplitude, IEMG and RMS were both statistically significant（all P〈0.05）. According to the inter-group comparison after acupuncture, the mean value of electromyography amplitude, variation rate of electromyography amplitude, IEMG and RMS varied in different degrees, however, the differences were not significant（all P〉0.05）; there was no significant difference in the total effective rate among the three groups（P〉0.05）. Conclusion Acupuncture treatment in different acupoint combinations can increase IEMG and RMS and reduce mean value of electromyography amplitude and variation rate of electromyography amplitude, enhance cervical vertebral stability and active contractility of muscle fiber, and improve the fatigue resistance of neck flexion; while, the therapeutic effect of acupuncture on cervical spondylosis has nothing to do with the distance or the number of selected acupoint.展开更多
Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the curr...Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the current understanding of the bidirectional relationship between blood-brain barrier disruption and neuroinflammation in traumatic brain injury,along with emerging combination therapeutic strategies.Literature review indicates that blood-brain barrier disruption and neuroinflammatory responses are key pathological features following traumatic brain injury.In the acute phase after traumatic brain injury,the pathological characteristics include primary blood-brain barrier disruption and the activation of inflammatory cascades.In the subacute phase,the pathological features are characterized by repair mechanisms and inflammatory modulation.In the chronic phase,the pathological features show persistent low-grade inflammation and incomplete recovery of the blood-brain barrier.Various physiological changes,such as structural alterations of the blood-brain barrier,inflammatory cascades,and extracellular matrix remodeling,interact with each other and are influenced by genetic,age,sex,and environmental factors.The dynamic balance between blood-brain barrier permeability and neuroinflammation is regulated by hormones,particularly sex hormones and stress-related hormones.Additionally,the role of gastrointestinal hormones is receiving increasing attention.Current treatment strategies for traumatic brain injury include various methods such as conventional drug combinations,multimodality neuromonitoring,hyperbaric oxygen therapy,and non-invasive brain stimulation.Artificial intelligence also shows potential in treatment decision-making and personalized therapy.Emerging sequential combination strategies and precision medicine approaches can help improve treatment outcomes;however,challenges remain,such as inadequate research on the mechanisms of the chronic phase traumatic brain injury and difficulties with technology integration.Future research on traumatic brain injury should focus on personalized treatment strategies,the standardization of techniques,costeffectiveness evaluations,and addressing the needs of patients with comorbidities.A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.展开更多
During 2000-2013, totally ten high-amylose specific hybrid rice combinations approved and five combinations for production test were bred in Sichuan Province. In the paper, rice yield, economic traits, quality indicat...During 2000-2013, totally ten high-amylose specific hybrid rice combinations approved and five combinations for production test were bred in Sichuan Province. In the paper, rice yield, economic traits, quality indicators and rice blast-resistance identification results of these 15 hybrid combinations were described and analyzed. Results show that Chuanxiangyou37 and Tianlongyou540 have relatively high amylose content, good yielding ability, high resistance and appropriate growth period, which are new hybrid rice varieties with organic combination of high amylase content, high gel consistency, high yield, stable yield and wide adaptability. Therefore, Chuanxiangyou37 and Tianlongyou540 are recommended as the main combination for rice production.展开更多
Background:Human skin is affected by ultraviolet rays on a daily basis,and excessive ultraviolet radiation(UVR)can lead to sunburn erythema,tanning,photoaging,and skin tumors.The combination of Astragali Radix(AR)and ...Background:Human skin is affected by ultraviolet rays on a daily basis,and excessive ultraviolet radiation(UVR)can lead to sunburn erythema,tanning,photoaging,and skin tumors.The combination of Astragali Radix(AR)and Anemarrhenae Rhizoma(AAR)is a common pairing in traditional Chinese medicine(TCM).According to earlier studies,they possess properties capable of alleviating the adverse impacts of UVR on the skin.However,the specific actions and underlying mechanisms require further investigation.The study aims to analyze the efficacy of AR-AAR in preventing UVR-induced skin damage and to clarify the associated molecular mechanisms.Methods:Potential signaling pathways by which AR and AAR may protect against UVR-induced skin damage were identified with network pharmacology,molecular docking techniques and molecular dynamics(MD)simulation.Except the normal group,the back skin of SD rats was exposed to 1.1 mW/cm^(2) UVA combined with 0.1 mW/cm^(2) UVB daily,and the UVR skin damage model was established.Morphological features of skin tissues of different groups were discovered through Hematoxylin and Eosin(HE)staining,Masson staining,Weigert staining.ELISA was utilized to measure the levels of reactive oxygen species(ROS),Interleukin 6(IL-6),Interleukin 1β(IL-1β)and Tumor necrosis factos-α(TNF-α)in skin tissues.RT-PCR and Western blot were employed to quantify the mRNA and protein contents of PI3K,AKT,and MMP-9.Results:Network pharmacology analysis predicts that AR-AAR may improve skin damage induced by UVR through the PI3K/AKT signaling pathway.Histological staining shows that AR-AAR can significantly reduce inflammatory infiltration and fibrosis in damaged skin.Treatment with AR-AAR(2:1)significantly reduced the expression levels of IL-1β,IL-6,TNF-αand ROS in UVR-damaged rat skin.After treatment with AR-AAR(2:1),not only did the relative mRNA expression levels of PI3K and AKT and the protein expression levels of PI3K,AKT,P-PI3K,and P-AKT increase,but the mRNA and protein expression levels of MMP-9 decreased.Conclusion:The study indicate that the AR-AAR combination and its active components may mitigate UVR skin damage by modulating the PI3K/AKT signaling pathway.展开更多
Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and...Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and resources,adding a substantial burden to the healthcare system and patients'families.In this context,chondroitinase ABC,a bacterial enzyme isolated from Proteus vulgaris that is modified to facilitate expression and secretion in mammals,has emerged as a promising therapeutic agent.It works by degrading chondroitin sulfate proteoglycans,cleaving the glycosaminoglycanchains of chondroitin sulfate proteoglycans into soluble disaccharides or tetrasaccharides.Chondroitin sulfate proteoglycans are potent axon growth inhibitors and principal constituents of the extracellular matrix surrounding glial and neuronal cells attached to glycosaminoglycan chains.Chondroitinase ABC has been shown to play an effective role in promoting recovery from acute and chronic spinal cord injury by improving axonal regeneration and sprouting,enhancing the plasticity of perineuronal nets,inhibiting neuronal apoptosis,and modulating immune responses in various animal models.In this review,we introduce the classification and pathological mechanisms of spinal cord injury and discuss the pathophysiological role of chondroitin sulfate proteoglycans in spinal cord injury.We also highlight research advancements in spinal cord injury treatment strategies,with a focus on chondroitinase ABC,and illustrate how improvements in chondroitinase ABC stability,enzymatic activity,and delivery methods have enhanced injured spinal cord repair.Furthermore,we emphasize that combination treatment with chondroitinase ABC further enhances therapeutic efficacy.This review aimed to provide a comprehensive understanding of the current trends and future directions of chondroitinase ABC-based spinal cord injury therapies,with an emphasis on how modern technologies are accelerating the optimization of chondroitinase ABC development.展开更多
Programmed cell death 1（PD-1）/programmed cell death 1 ligand（PD-L1） blockade has shown promising effects in cancer immunotherapy. Removing the so-called ＂brakes＂ on T cell immune responses by blocking the PD-1/P...Programmed cell death 1（PD-1）/programmed cell death 1 ligand（PD-L1） blockade has shown promising effects in cancer immunotherapy. Removing the so-called ＂brakes＂ on T cell immune responses by blocking the PD-1/PDL1 check point should boost anti-tumor immunity and provide durable tumor regression for cancer patients.However, 30%–60% of patients show no response to PD-1/PD-L1 blockade. Thus, it is urgent to explore the underlying resistance mechanisms to improve sensitivity to anti-PD-1/PD-L1 therapy. We propose that the mechanisms promoting resistance mainly include T cell exclusion or exhaustion at the tumor site,immunosuppressive factors in the tumor microenvironment（TME）, and a range of tumor-intrinsic factors. This review highlights the power of studying the cellular and molecular mechanisms of resistance to improve the rational design of combination therapeutic strategies that can be translated to the clinic. Here, we briefly discuss the development of PD-1/PD-L1 blockade agents and focus on the current issues and future prospects for potential combinatorial therapeutic strategies that include anti-PD-1/PD-L1 therapy, based upon the available preclinical and clinical data.展开更多
Tackling the problems of underground water storage in collieries in arid regions requires knowledge of the effect of water intrusion and loading rate on the mechanical properties of and crack development in coal–rock...Tackling the problems of underground water storage in collieries in arid regions requires knowledge of the effect of water intrusion and loading rate on the mechanical properties of and crack development in coal–rock combinations. Fifty-four coal–rock combinations were prepared and split equally into groups containing different moisture contents(dry, natural moisture and saturated) to conduct acoustic emission testing under uniaxial compression with loading rates ranging from 0.1 mm/min to 0.6 mm/min. The results show that the peak stress and strength-softening modulus, elastic modulus, strain-softening modulus, and post-peak modulus partly decrease with increasing moisture content and loading rate. In contrast, peak strain increases with increasing moisture content and fluctuates with rising loading rate. More significantly, the relationship between stiffness and stress, combined with accumulated counts of acoustic emission, can be used to precisely predict all phases of crack propagation. This is helpful in studying the impact of moisture content and loading rate on crack propagation and accurately calculating mechanical properties. We also determined that the stress thresholds of crack closure, crack initiation, and crack damage do not vary with changes of moisture content and loading rate, constituting 15.22%, 32.20%, and 80.98% of peak stress, respectively. These outcomes assist in developing approaches to water storage in coal mines, determining the necessary width of waterproof coal–rock pillars, and methods of supporting water-enriched roadways, while also advances understanding the mechanical properties of coal–rock combinations and laws of crack propagation.展开更多
目的:探讨髓芯减压联合不同治疗策略对早中期股骨头坏死患者的疗效及安全性评价。方法:系统检索PubMed、Web of Science、Cochrane Library、EMbase、中国知网、维普、万方和中国生物医学文献数据库,纳入截至2025-01-19发表的关于髓芯...目的:探讨髓芯减压联合不同治疗策略对早中期股骨头坏死患者的疗效及安全性评价。方法:系统检索PubMed、Web of Science、Cochrane Library、EMbase、中国知网、维普、万方和中国生物医学文献数据库,纳入截至2025-01-19发表的关于髓芯减压联合治疗早中期股骨头坏死的随机对照试验。采用Cochrane偏倚风险评估工具对文献质量进行评价,运用GRADE系统评价证据等级,基于贝叶斯框架构建网状Meta分析模型。采用标准化均数差进行效应估计,结果以累积排序概率曲线下面积进行干预优效性排序。敏感性分析采用逐项剔除法评估模型稳健性,并通过基线协变量评估传递性假设。结果:最终纳入73项随机对照试验,共计5148例患者、5777个髋关节,涵盖15种联合治疗方法。结果显示:①在提高综合临床疗效方面,髓芯减压联合自体骨髓单核细胞浓缩注射、骨髓间充质干细胞移植、支撑性植骨及补肾活血类中药复方汤剂等均优于单纯髓芯减压,其中髓芯减压联合自体骨髓单核细胞浓缩注射显示出最优的干预效果(累积排序概率曲线下面积=96.23%);②在髋关节功能改善方面,髓芯减压联合中医药序贯治疗疗效最优(累积排序概率曲线下面积=93.85%);③在疼痛缓解方面,髓芯减压联合中成药(补肾活血+活血化瘀)与活血化瘀类中药复方汤剂效果突出;④在影像学改善方面,髓芯减压联合自体源性干细胞局部植入效果最佳(累积排序概率曲线下面积=82.56%);⑤在临床安全性方面,髓芯减压联合活血化瘀类中药复方汤剂在降低不良事件发生率方面具有相对优势(P<0.05)。为评估结果稳健性,采用逐项剔除法进行敏感性分析,显示模型稳定,主要干预结果对单项研究不敏感,传递性假设成立。结论:髓芯减压联合干细胞移植、中医药序贯治疗等多种治疗方案在改善早中期股骨头坏死临床疗效方面优于单纯髓芯减压,表现为关节功能保护、结构重建与疼痛控制等多重优势。考虑部分干预文献数量有限及研究质量差异,仍需高质量、多中心、大样本随机对照试验进一步验证。展开更多
There have been exponential gains in immuno-oncology in recent times through the development of immune checkpoint inhibitors. Already approved by the U.S. Food and Drug Administration for advanced melanoma and non-sma...There have been exponential gains in immuno-oncology in recent times through the development of immune checkpoint inhibitors. Already approved by the U.S. Food and Drug Administration for advanced melanoma and non-small cell lung cancer,immune checkpoint inhibitors also appears to have significant antitumor activity in multiple other tumor types. An exciting component of immunotherapy is the durability of antitumor responses observed, with some patients achieving disease control for many years. Nevertheless, not all patients benefit, and efforts should thus now focus on improving the efficacy of immunotherapy through the use of combination approaches and predictive biomarkers of response and resistance. There are multiple potential rational combinations using an immunotherapy backbone, including existing treatments such as radiotherapy, chemotherapy or molecularly targeted agents, as well as other immunotherapeutics. The aim of such antitumor strategies will be to raise the tail on the survival curve by increasing the number of long term survivors, while managing any additive or synergistic toxicities that may arise with immunotherapy combinations. Rational trial designs based on a clear understanding of tumor biology and drug pharmacology remain paramount. This article reviews the biology underpinning immuno-oncology, discusses existing and novel immunotherapeutic combinations currently in development, the challenges of predictive biomarkers of response and resistance and the impact of immuno-oncology on early phase clinical trial design.展开更多
Background:Nonalcoholic fatty liver disease and its advanced stage,nonalcoholic steatohepatitis(NASH),are the major cause of hepatocellular carcinoma(HCC)and other end-stage liver disease.However,the potential mechani...Background:Nonalcoholic fatty liver disease and its advanced stage,nonalcoholic steatohepatitis(NASH),are the major cause of hepatocellular carcinoma(HCC)and other end-stage liver disease.However,the potential mechanism and therapeutic strategies have not been clarified.This study aimed to identify potential roles of mi RNA/m RNA axis in the pathogenesis and drug combinations in the treatment of NASH.Methods:Microarray GSE59045 and GSE48452 were downloaded from the Gene Expression Omnibus and analyzed using R.Then we obtained differentially expressed genes(DE-genes).DAVID database was used for Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment pathway analysis.Protein-protein interaction(PPI)networks were used for the identification of hub genes.We found upstream regulators of hub genes using mi RTar Base.The expression and correlation of key mi RNA and its targets were detected by q PCR.Drug Pair Seeker was employed to predict drug combinations against NASH.The expression of mi RNA and hub genes in HCC was identified in the Cancer Genome Atlas database and Human Protein Atlas database.Results:Ninety-four DE-genes were accessed.GO and KEGG analysis showed that these predicted genes were linked to lipid metabolism.Eleven genes were identified as hub genes in PPI networks,and they were highly expressed in cells with vigorous lipid metabolism.hsa-mi R-335-5 p was the upstream regulator of 9 genes in the 11 hub genes,and it was identified as a key mi RNA.The hub genes were highly expressed in NASH models,while hsa-mi R-335-5 p was lowly expressed.The correlation of mi RNA-m RNA was established by q PCR.Functional verification indicated that hsa-mi R-335-5 p had inhibitory effect on the development of NASH.Finally,drug combinations were predicted and the expression of mi RNA and hub genes in HCC was identified.Conclusions:In the study,potential mi RNA-m RNA pathways related to NASH were identified.Targeting these pathways may be novel strategies against NASH.展开更多
The invertibility of combinations of two orthogonal projectors aP ＋ bQ - cPQ - dQP is researched by using the CSdecomposition of matrices and properties of orthogonal projectors. The Moore-enrose inverse of the combi...The invertibility of combinations of two orthogonal projectors aP ＋ bQ - cPQ - dQP is researched by using the CSdecomposition of matrices and properties of orthogonal projectors. The Moore-enrose inverse of the combinations is presented under some special conditions.展开更多
Multi-drug(or multi-element)combinations are often prescribed in the practice of clinical medicine and as foods for special medical purposes.The main motivations for these combinations are that most diseases contain m...Multi-drug(or multi-element)combinations are often prescribed in the practice of clinical medicine and as foods for special medical purposes.The main motivations for these combinations are that most diseases contain multiple related targets and an appropriate combination can maximize benefits while minimizing adverse reactions.As such,it is especially important to derive mathematical models for their quantitative calculation.In this paper,we introduce mathematical rules for the synergistic,additive,and antagonistic effects of multi-drug combinations developed in our laboratory.We have established a“onebelt,one-line”model and provide examples of the quantitative calculation of the synergistic,additive,and antagonistic effects of a combination of multiple components.We also explain how to scientifically and precisely determine the intensity of these synergies,additions and antagonisms,as well as their corresponding dose ranges,thereby laying a solid theoretical foundation for market listing combinatorial drugs and foods for special medical purposes.展开更多
GPS positioning precision is affected by various error sources, and traditional combinations of GPS carrier phase observations have their own limitations such as the wide-lane, the narrow-lane and the ionospheric-free...GPS positioning precision is affected by various error sources, and traditional combinations of GPS carrier phase observations have their own limitations such as the wide-lane, the narrow-lane and the ionospheric-free combinations. To obtain the optimal positioning precision, a new linear combination method is addressed through the variance-covariance （VCV） of the GPS multi-frequency carrier phase combination equations, and the impact of the positioning precision is analyzed with the changing of the observation errors deduced by the law of error propagation. For the high precision positioning with only one carrier phase combination, the optimal combination method is deduced and further validated by an example of a baseline resolution with 60 km length. The result indicates that this method is the simplest, and the positioning precision is the best. Therefore, it is useful for long baseline quick positioning for different precision requirements in various distances.展开更多
Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States,with poor response to current standard of care,short progression-free and overall survival.Immunotherapies th...Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States,with poor response to current standard of care,short progression-free and overall survival.Immunotherapies that target cytotoxic T lymphocyte antigen-4,programmed cell death protein-1,and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma,renal cell carcinoma,and nonsmall cell lung cancer due to high numbers of somatic mutations,combined with cytotoxic T-cell responses.However,single checkpoint blockade was ineffective in pancreatic cancer,highlighting the challenges including the poor antigenicity,a dense desmoplastic stroma,and a largely immunosuppressive microenvironment.In this review,we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy,radiotherapy,and targeted therapy.These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.展开更多
基金supported by grants from the Chinese Academy of Sciences(XDA24010101)the Biological Breeding-National Science and Technology Major Project(2024ZD04077)+2 种基金the National Key Research and Development Program of China(2023YFF1001200)Natural Science Foundation of Zhejiang Province(LD24C130001)the Agricultural Science and Technology Innovation Program(ASTIP)of CAAS。
文摘A later heading date generally leads to higher grain yield in favorable ecological regions;however,grain yield reaches a limit as the heading date exceeds a certain threshold.Ghd7 is the first cloned major gene that regulates heading date,plant height and grain number.Here,we investigated the relationship between Ghd7 and florigen genes Hd3a and RFT1,to determine their roles in regulating heading date and grain number under different photoperiods.Our results revealed that under long-day(LD)conditions,Hd3a acts prior to RFT1 to promote heading while negatively regulating plant height and grain number.In contrast,Ghd7 positively regulates heading date,plant height,and grain number by inhibiting both Hd3a and RFT1.Under short-day(SD)conditions,the functions of Hd3a and RFT1 remain consistent with those under LD conditions,but Ghd7 does not inhibit their expression,resulting in a weaker phenotypic effect compared to Hd3a.Additionally,under both LD and SD conditions,increased Ghd7 expression enhances its inhibitory effect on Hd3a and RFT1,leading to later heading and increased grain number;however,once the heading date exceeds 94 d,grain number no longer increases.Moreover,the gn1a allele increased grain number by 16.5%to 42.5%,while combinations of the elite alleles from Ghd7,Hd3a,RFT1,and Gn1a significantly increased grain number by up to 240.9%.Therefore,we propose a new breeding strategy to optimize the heading date and grain number using the Ghd7Hd3aRFT1gn1a combination of Ghd7,Hd3a,RFT1,and Gn1a under LD conditions,and the Ghd7hd3aRFT1gn1a combination under SD conditions.This strategy improved the yield of the high-quality Northeast variety Kongyu 131(KY131)by 69.1%in Beijing and 93.7%in Hainan.This strategy will greatly improve the efficiency of north-to-south adaptation in rice,providing theoretical guidance for expanding the geographical adaptability of rice varieties.
基金supported by National Science Foundations of China(Grant No.11771340,12171373).
文摘Recently,Choe-Koo-Wang(J Funct Anal,2020,278)demonstrated the rigid phenomenon:The compact linear combination of composition operators under the Coefficient Non-cancellation Condition(CNC),implies that each difference is compact on the weighted Bergman space in the unit disk.Motivated by the subtle connection of composition operator theory on the weighted Bergman spaces,Korenblum spaces and bounded holomorphic function spaces,we first explore the rigid phenomenon which also holds on the Korenblum space over the unit ball.Furthermore,we discuss which difference of composition operators is compact when the compact combination of composition operators does not satisfy the condition(CNC)on Korenblum spaces and bounded holomorphic function spaces over the unit ball setting.
基金Financial support from the National Natural Science Foundation of China(Grant No.52374119)the Province Education Department of Liaoning(Grant No.LJ212410146068)the opening fund of State Key Laboratory of Performance Monitoring and Protecting of Rail Transit Infrastructure,East China Jiaotong University(Grant No.HJGZ2023103).
文摘Understanding the mechanical properties of coal-rock-bolt(CRB)combinations at high strain rates and the anchoring mechanism of bolts is crucial for ensuring the safety of coal mining operations.However,the dynamic behaviors of these combinations,especially the mechanism of action of prestressed bolts,still need to be further investigated.This study carried out split Hopkinson pressure bar(SHPB)tests on three sets of coal-rock(CR),CRB,and coal-rock-prestressed bolt(CRPB)combinations with different interface angles(β=15°,30°,45°,and 60°).The dynamic properties of the combinations were analyzed based on the stress-strain curve,energy dissipation,dynamic strength,fractal dimension of cracks,and failure mode of bolts.The test results show that a larger β will affect the stress transfer and anti-sliding ability of CR,resulting in a decrease in CR strength.The anchoring force of the bolt effectively suppresses the slip feature of CRB at the yield stage.As the strain rate increases,CRB shows a more pronounced'sudden increase'in strength,and the bolt significantly enhances its dynamic strength.The prestressed bolts enhance the dynamic strength of CRPB while weaken the effect of β.The fractal dimension of the macrocracks increases with strain rate,with smaller variations in CRB and CRPB,indicating that the bolt reduces the complexity degree of CRB and CRPB.The anchoring force of CRB depends on bolt strength,which reduces the slip along the interface.The anchoring force of CRPB balances the coal-rock slip and suppresses crack formation,resulting in a more cohesive response under dynamic load.
基金supported by the National Natural Science Foundation of China(No.52274026)the National Key Research and Development Program(No.2022YFC2806504)the CNOOC Research Project(No.KJGG-2022-17-04 and NO.KJGG-2022-17-05).
文摘Effective isolation between the cement sheath and the sandstone is crucial for the development and production of oil and gas wells in sandstone formations.In this study,a cement-sandstone composite(CSC)was prepared,and based onμ-CT three-dimensional reconstruction imaging and finite element analysis(FEA)techniques,the stress distribution and potential failure mechanism at the cement-sandstone bonding interface under axial loading were analyzed.The key findings are as follows:(1)stress concentrations are highly likely to form at the gap between the cement and sandstone interface and around interfacial voids,with Von Mises stress reaching critical levels of 18.0-20.0 MPa at these locations,significantly exceeding the stress magnitudes in well-bonded regions;(2)the phenomenon of local stress concentration driven by interfacial defects can be identified as the main basis for predicting damage location in interfacial debonding and continuous shear under axial load;(3)ensuring tight cementation at the cement-sandstone interface and minimizing interfacial voids are paramount for preventing stress-induced failure;(4)the critical Von Mises stress value of 20 MPa at the interface defect can be used as a benchmark for material selection and designed to ensure long-term integrity in oil and gas well applications subjected to similar axial loads.These findings contribute to a more accurate understanding of the failure mechanism of the cement-sandstone interface and to the precise design of material properties,thereby ensuring the long-term integrity of oil and gas well applications subjected to similar axial loads.
基金Supported by “The 12th five-year plan” programmed project of educational science in Hubei Province:2014B095
文摘Objective To observe the influence of different acupoint combinations on immediate effect of surface electromyography of patients with cervical spondylosis, and to explore the interactions and laws among different acupoint combinations. Methods Acupuncture in three kinds of different acupoint combinations was conducted on 90 patients with cervical spondylosis（three groups）： group A [distal point selection group： Kūnlún（昆仑 BL 60） and Hòuxī（后溪 SI 3）]; group B [local point selection group： Fēngchí（风池 GB 20） and Tiānzhù（天柱 BL 10）]; group C（distal and local point selection group： BL 60, SI 3, GB 20 and BL 10）. Self control before and after treatment was adopted to observe the mean value of surface electromyography（SEMG） amplitude, to measure the mean values of integrated electromyography（IEMG） and electromyography root mean square（RMS）, and to calculate the variation rate of electromyography amplitude of trapezius on the affected side of patients before and after acupuncture. The differences of influences of different acupoint combinations on immediate effect of surface electromyography were compared intra-group, and the differences among the three groups after acupuncture were also compared. Results According to the intragroup comparison before and after acupuncture, the differences of mean value of electromyography amplitude, variation rate of electromyography amplitude, IEMG and RMS were both statistically significant（all P〈0.05）. According to the inter-group comparison after acupuncture, the mean value of electromyography amplitude, variation rate of electromyography amplitude, IEMG and RMS varied in different degrees, however, the differences were not significant（all P〉0.05）; there was no significant difference in the total effective rate among the three groups（P〉0.05）. Conclusion Acupuncture treatment in different acupoint combinations can increase IEMG and RMS and reduce mean value of electromyography amplitude and variation rate of electromyography amplitude, enhance cervical vertebral stability and active contractility of muscle fiber, and improve the fatigue resistance of neck flexion; while, the therapeutic effect of acupuncture on cervical spondylosis has nothing to do with the distance or the number of selected acupoint.
基金supported by Open Scientific Research Program of Military Logistics,No.BLB20J009(to YZhao).
文摘Blood-brain barrier disruption and the neuroinflammatory response are significant pathological features that critically influence disease progression and treatment outcomes.This review systematically analyzes the current understanding of the bidirectional relationship between blood-brain barrier disruption and neuroinflammation in traumatic brain injury,along with emerging combination therapeutic strategies.Literature review indicates that blood-brain barrier disruption and neuroinflammatory responses are key pathological features following traumatic brain injury.In the acute phase after traumatic brain injury,the pathological characteristics include primary blood-brain barrier disruption and the activation of inflammatory cascades.In the subacute phase,the pathological features are characterized by repair mechanisms and inflammatory modulation.In the chronic phase,the pathological features show persistent low-grade inflammation and incomplete recovery of the blood-brain barrier.Various physiological changes,such as structural alterations of the blood-brain barrier,inflammatory cascades,and extracellular matrix remodeling,interact with each other and are influenced by genetic,age,sex,and environmental factors.The dynamic balance between blood-brain barrier permeability and neuroinflammation is regulated by hormones,particularly sex hormones and stress-related hormones.Additionally,the role of gastrointestinal hormones is receiving increasing attention.Current treatment strategies for traumatic brain injury include various methods such as conventional drug combinations,multimodality neuromonitoring,hyperbaric oxygen therapy,and non-invasive brain stimulation.Artificial intelligence also shows potential in treatment decision-making and personalized therapy.Emerging sequential combination strategies and precision medicine approaches can help improve treatment outcomes;however,challenges remain,such as inadequate research on the mechanisms of the chronic phase traumatic brain injury and difficulties with technology integration.Future research on traumatic brain injury should focus on personalized treatment strategies,the standardization of techniques,costeffectiveness evaluations,and addressing the needs of patients with comorbidities.A multidisciplinary approach should be used to enhance treatment and improve patient outcomes.
基金Supported by Financial Genetic Engineering Program of Sichuan Province during the 12th Five-Year Plan Period(2011JYGC11-029)Sichuan Innovation Team Program of National Modern Agricultural Industry Technology System of China+1 种基金Rice Breeding Program of Sichuan Province during the 12th Five-Year Plan Period(2011NZ-0098-1)Major Scientific and Technological Project of Luzhou City(2011-N-09)~~
文摘During 2000-2013, totally ten high-amylose specific hybrid rice combinations approved and five combinations for production test were bred in Sichuan Province. In the paper, rice yield, economic traits, quality indicators and rice blast-resistance identification results of these 15 hybrid combinations were described and analyzed. Results show that Chuanxiangyou37 and Tianlongyou540 have relatively high amylose content, good yielding ability, high resistance and appropriate growth period, which are new hybrid rice varieties with organic combination of high amylase content, high gel consistency, high yield, stable yield and wide adaptability. Therefore, Chuanxiangyou37 and Tianlongyou540 are recommended as the main combination for rice production.
基金supported by the Shaanxi Qinchuang Yuan“scientist+engineer”team construction(No.2023KXJ-080)Shaanxi Chiral Drug Engineering Technology Research Center(Department of Science and Technology of Shaanxi Province.No.[2011]-251).
文摘Background:Human skin is affected by ultraviolet rays on a daily basis,and excessive ultraviolet radiation(UVR)can lead to sunburn erythema,tanning,photoaging,and skin tumors.The combination of Astragali Radix(AR)and Anemarrhenae Rhizoma(AAR)is a common pairing in traditional Chinese medicine(TCM).According to earlier studies,they possess properties capable of alleviating the adverse impacts of UVR on the skin.However,the specific actions and underlying mechanisms require further investigation.The study aims to analyze the efficacy of AR-AAR in preventing UVR-induced skin damage and to clarify the associated molecular mechanisms.Methods:Potential signaling pathways by which AR and AAR may protect against UVR-induced skin damage were identified with network pharmacology,molecular docking techniques and molecular dynamics(MD)simulation.Except the normal group,the back skin of SD rats was exposed to 1.1 mW/cm^(2) UVA combined with 0.1 mW/cm^(2) UVB daily,and the UVR skin damage model was established.Morphological features of skin tissues of different groups were discovered through Hematoxylin and Eosin(HE)staining,Masson staining,Weigert staining.ELISA was utilized to measure the levels of reactive oxygen species(ROS),Interleukin 6(IL-6),Interleukin 1β(IL-1β)and Tumor necrosis factos-α(TNF-α)in skin tissues.RT-PCR and Western blot were employed to quantify the mRNA and protein contents of PI3K,AKT,and MMP-9.Results:Network pharmacology analysis predicts that AR-AAR may improve skin damage induced by UVR through the PI3K/AKT signaling pathway.Histological staining shows that AR-AAR can significantly reduce inflammatory infiltration and fibrosis in damaged skin.Treatment with AR-AAR(2:1)significantly reduced the expression levels of IL-1β,IL-6,TNF-αand ROS in UVR-damaged rat skin.After treatment with AR-AAR(2:1),not only did the relative mRNA expression levels of PI3K and AKT and the protein expression levels of PI3K,AKT,P-PI3K,and P-AKT increase,but the mRNA and protein expression levels of MMP-9 decreased.Conclusion:The study indicate that the AR-AAR combination and its active components may mitigate UVR skin damage by modulating the PI3K/AKT signaling pathway.
基金supported by the National Natural Science Foundation of China,No.82002645China Postdoctoral Science Foundation,No.2022M722321Jiangsu Funding Program for Excellent Postdoctoral Talent,No.2022ZB552(all to YH)。
文摘Spinal cord injuries have overwhelming physical and occupational implications for patients.Moreover,the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and resources,adding a substantial burden to the healthcare system and patients'families.In this context,chondroitinase ABC,a bacterial enzyme isolated from Proteus vulgaris that is modified to facilitate expression and secretion in mammals,has emerged as a promising therapeutic agent.It works by degrading chondroitin sulfate proteoglycans,cleaving the glycosaminoglycanchains of chondroitin sulfate proteoglycans into soluble disaccharides or tetrasaccharides.Chondroitin sulfate proteoglycans are potent axon growth inhibitors and principal constituents of the extracellular matrix surrounding glial and neuronal cells attached to glycosaminoglycan chains.Chondroitinase ABC has been shown to play an effective role in promoting recovery from acute and chronic spinal cord injury by improving axonal regeneration and sprouting,enhancing the plasticity of perineuronal nets,inhibiting neuronal apoptosis,and modulating immune responses in various animal models.In this review,we introduce the classification and pathological mechanisms of spinal cord injury and discuss the pathophysiological role of chondroitin sulfate proteoglycans in spinal cord injury.We also highlight research advancements in spinal cord injury treatment strategies,with a focus on chondroitinase ABC,and illustrate how improvements in chondroitinase ABC stability,enzymatic activity,and delivery methods have enhanced injured spinal cord repair.Furthermore,we emphasize that combination treatment with chondroitinase ABC further enhances therapeutic efficacy.This review aimed to provide a comprehensive understanding of the current trends and future directions of chondroitinase ABC-based spinal cord injury therapies,with an emphasis on how modern technologies are accelerating the optimization of chondroitinase ABC development.
基金supported by grants from the National Natural Science Foundation of China (No. 81171986)the Ministry of Public Health (No. 201501004)
文摘Programmed cell death 1（PD-1）/programmed cell death 1 ligand（PD-L1） blockade has shown promising effects in cancer immunotherapy. Removing the so-called ＂brakes＂ on T cell immune responses by blocking the PD-1/PDL1 check point should boost anti-tumor immunity and provide durable tumor regression for cancer patients.However, 30%–60% of patients show no response to PD-1/PD-L1 blockade. Thus, it is urgent to explore the underlying resistance mechanisms to improve sensitivity to anti-PD-1/PD-L1 therapy. We propose that the mechanisms promoting resistance mainly include T cell exclusion or exhaustion at the tumor site,immunosuppressive factors in the tumor microenvironment（TME）, and a range of tumor-intrinsic factors. This review highlights the power of studying the cellular and molecular mechanisms of resistance to improve the rational design of combination therapeutic strategies that can be translated to the clinic. Here, we briefly discuss the development of PD-1/PD-L1 blockade agents and focus on the current issues and future prospects for potential combinatorial therapeutic strategies that include anti-PD-1/PD-L1 therapy, based upon the available preclinical and clinical data.
基金Project(2014QNB31)supported by the Fundamental Research Funds for the Central Universities,ChinaProjects(51674248)supported by the National Natural Science Foundation of ChinaProject supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),China
文摘Tackling the problems of underground water storage in collieries in arid regions requires knowledge of the effect of water intrusion and loading rate on the mechanical properties of and crack development in coal–rock combinations. Fifty-four coal–rock combinations were prepared and split equally into groups containing different moisture contents(dry, natural moisture and saturated) to conduct acoustic emission testing under uniaxial compression with loading rates ranging from 0.1 mm/min to 0.6 mm/min. The results show that the peak stress and strength-softening modulus, elastic modulus, strain-softening modulus, and post-peak modulus partly decrease with increasing moisture content and loading rate. In contrast, peak strain increases with increasing moisture content and fluctuates with rising loading rate. More significantly, the relationship between stiffness and stress, combined with accumulated counts of acoustic emission, can be used to precisely predict all phases of crack propagation. This is helpful in studying the impact of moisture content and loading rate on crack propagation and accurately calculating mechanical properties. We also determined that the stress thresholds of crack closure, crack initiation, and crack damage do not vary with changes of moisture content and loading rate, constituting 15.22%, 32.20%, and 80.98% of peak stress, respectively. These outcomes assist in developing approaches to water storage in coal mines, determining the necessary width of waterproof coal–rock pillars, and methods of supporting water-enriched roadways, while also advances understanding the mechanical properties of coal–rock combinations and laws of crack propagation.
文摘目的:探讨髓芯减压联合不同治疗策略对早中期股骨头坏死患者的疗效及安全性评价。方法:系统检索PubMed、Web of Science、Cochrane Library、EMbase、中国知网、维普、万方和中国生物医学文献数据库,纳入截至2025-01-19发表的关于髓芯减压联合治疗早中期股骨头坏死的随机对照试验。采用Cochrane偏倚风险评估工具对文献质量进行评价,运用GRADE系统评价证据等级,基于贝叶斯框架构建网状Meta分析模型。采用标准化均数差进行效应估计,结果以累积排序概率曲线下面积进行干预优效性排序。敏感性分析采用逐项剔除法评估模型稳健性,并通过基线协变量评估传递性假设。结果:最终纳入73项随机对照试验,共计5148例患者、5777个髋关节,涵盖15种联合治疗方法。结果显示:①在提高综合临床疗效方面,髓芯减压联合自体骨髓单核细胞浓缩注射、骨髓间充质干细胞移植、支撑性植骨及补肾活血类中药复方汤剂等均优于单纯髓芯减压,其中髓芯减压联合自体骨髓单核细胞浓缩注射显示出最优的干预效果(累积排序概率曲线下面积=96.23%);②在髋关节功能改善方面,髓芯减压联合中医药序贯治疗疗效最优(累积排序概率曲线下面积=93.85%);③在疼痛缓解方面,髓芯减压联合中成药(补肾活血+活血化瘀)与活血化瘀类中药复方汤剂效果突出;④在影像学改善方面,髓芯减压联合自体源性干细胞局部植入效果最佳(累积排序概率曲线下面积=82.56%);⑤在临床安全性方面,髓芯减压联合活血化瘀类中药复方汤剂在降低不良事件发生率方面具有相对优势(P<0.05)。为评估结果稳健性,采用逐项剔除法进行敏感性分析,显示模型稳定,主要干预结果对单项研究不敏感,传递性假设成立。结论:髓芯减压联合干细胞移植、中医药序贯治疗等多种治疗方案在改善早中期股骨头坏死临床疗效方面优于单纯髓芯减压,表现为关节功能保护、结构重建与疼痛控制等多重优势。考虑部分干预文献数量有限及研究质量差异,仍需高质量、多中心、大样本随机对照试验进一步验证。
文摘There have been exponential gains in immuno-oncology in recent times through the development of immune checkpoint inhibitors. Already approved by the U.S. Food and Drug Administration for advanced melanoma and non-small cell lung cancer,immune checkpoint inhibitors also appears to have significant antitumor activity in multiple other tumor types. An exciting component of immunotherapy is the durability of antitumor responses observed, with some patients achieving disease control for many years. Nevertheless, not all patients benefit, and efforts should thus now focus on improving the efficacy of immunotherapy through the use of combination approaches and predictive biomarkers of response and resistance. There are multiple potential rational combinations using an immunotherapy backbone, including existing treatments such as radiotherapy, chemotherapy or molecularly targeted agents, as well as other immunotherapeutics. The aim of such antitumor strategies will be to raise the tail on the survival curve by increasing the number of long term survivors, while managing any additive or synergistic toxicities that may arise with immunotherapy combinations. Rational trial designs based on a clear understanding of tumor biology and drug pharmacology remain paramount. This article reviews the biology underpinning immuno-oncology, discusses existing and novel immunotherapeutic combinations currently in development, the challenges of predictive biomarkers of response and resistance and the impact of immuno-oncology on early phase clinical trial design.
基金supported by grants from Key ProgramNational Natural Science Foundation of China(81930016)+3 种基金National Natural Science Foundation of China(81702858)Key Research&Development Plan of Zhejiang Province(2019C03050)National S&T Major Project(2017ZX10203205)National Natural Science Funds for Distinguished Young Scholar of China(81625003)。
文摘Background:Nonalcoholic fatty liver disease and its advanced stage,nonalcoholic steatohepatitis(NASH),are the major cause of hepatocellular carcinoma(HCC)and other end-stage liver disease.However,the potential mechanism and therapeutic strategies have not been clarified.This study aimed to identify potential roles of mi RNA/m RNA axis in the pathogenesis and drug combinations in the treatment of NASH.Methods:Microarray GSE59045 and GSE48452 were downloaded from the Gene Expression Omnibus and analyzed using R.Then we obtained differentially expressed genes(DE-genes).DAVID database was used for Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment pathway analysis.Protein-protein interaction(PPI)networks were used for the identification of hub genes.We found upstream regulators of hub genes using mi RTar Base.The expression and correlation of key mi RNA and its targets were detected by q PCR.Drug Pair Seeker was employed to predict drug combinations against NASH.The expression of mi RNA and hub genes in HCC was identified in the Cancer Genome Atlas database and Human Protein Atlas database.Results:Ninety-four DE-genes were accessed.GO and KEGG analysis showed that these predicted genes were linked to lipid metabolism.Eleven genes were identified as hub genes in PPI networks,and they were highly expressed in cells with vigorous lipid metabolism.hsa-mi R-335-5 p was the upstream regulator of 9 genes in the 11 hub genes,and it was identified as a key mi RNA.The hub genes were highly expressed in NASH models,while hsa-mi R-335-5 p was lowly expressed.The correlation of mi RNA-m RNA was established by q PCR.Functional verification indicated that hsa-mi R-335-5 p had inhibitory effect on the development of NASH.Finally,drug combinations were predicted and the expression of mi RNA and hub genes in HCC was identified.Conclusions:In the study,potential mi RNA-m RNA pathways related to NASH were identified.Targeting these pathways may be novel strategies against NASH.
基金Supported by the Hubei Normal University Research Grant (2008D54)
文摘The invertibility of combinations of two orthogonal projectors aP ＋ bQ - cPQ - dQP is researched by using the CSdecomposition of matrices and properties of orthogonal projectors. The Moore-enrose inverse of the combinations is presented under some special conditions.
文摘Multi-drug(or multi-element)combinations are often prescribed in the practice of clinical medicine and as foods for special medical purposes.The main motivations for these combinations are that most diseases contain multiple related targets and an appropriate combination can maximize benefits while minimizing adverse reactions.As such,it is especially important to derive mathematical models for their quantitative calculation.In this paper,we introduce mathematical rules for the synergistic,additive,and antagonistic effects of multi-drug combinations developed in our laboratory.We have established a“onebelt,one-line”model and provide examples of the quantitative calculation of the synergistic,additive,and antagonistic effects of a combination of multiple components.We also explain how to scientifically and precisely determine the intensity of these synergies,additions and antagonisms,as well as their corresponding dose ranges,thereby laying a solid theoretical foundation for market listing combinatorial drugs and foods for special medical purposes.
基金Supported by the Key Laboratory of Geological Hazards on Three Gorges Reservoir Area,Ministry of Education, China(No.2006KDZ05).
文摘GPS positioning precision is affected by various error sources, and traditional combinations of GPS carrier phase observations have their own limitations such as the wide-lane, the narrow-lane and the ionospheric-free combinations. To obtain the optimal positioning precision, a new linear combination method is addressed through the variance-covariance （VCV） of the GPS multi-frequency carrier phase combination equations, and the impact of the positioning precision is analyzed with the changing of the observation errors deduced by the law of error propagation. For the high precision positioning with only one carrier phase combination, the optimal combination method is deduced and further validated by an example of a baseline resolution with 60 km length. The result indicates that this method is the simplest, and the positioning precision is the best. Therefore, it is useful for long baseline quick positioning for different precision requirements in various distances.
文摘Pancreatic cancer is the third leading cause of cancer mortality in both men and women in the United States,with poor response to current standard of care,short progression-free and overall survival.Immunotherapies that target cytotoxic T lymphocyte antigen-4,programmed cell death protein-1,and programmed death-ligand 1 checkpoints have shown remarkable activities in several cancers such as melanoma,renal cell carcinoma,and nonsmall cell lung cancer due to high numbers of somatic mutations,combined with cytotoxic T-cell responses.However,single checkpoint blockade was ineffective in pancreatic cancer,highlighting the challenges including the poor antigenicity,a dense desmoplastic stroma,and a largely immunosuppressive microenvironment.In this review,we will summarize available clinical results and ongoing efforts of combining immune checkpoint therapies with other treatment modalities such as chemotherapy,radiotherapy,and targeted therapy.These combination therapies hold promise in unleashing the potential of immunotherapy in pancreatic cancer to achieve better and more durable clinical responses by enhancing cytotoxic T-cell responses.
